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RecruitingNCT04846933DECIDERUpdated Jan 16, 2025

Multi-layer Data to Improve Diagnosis, Predict Therapy Resistance and Suggest Targeted Therapies in HGSOC

An interventional study of WGS and RNA sequencing and circulating tumor DNA (ctDNA) in High Grade Ovarian Serous Adenocarcinoma and High Grade Serous Carcinoma, sponsored by Turku University Hospital. Recruiting at 1 site in Finland. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-01-16.

Sponsored by Turku University Hospital · Not applicable, Interventional, and Basic science

Phase
Not applicable
Study type
Interventional
Enrollment
200
Allocation
Non-randomized
Ages
18 Years and older
Sex
Female
01

Study summary

Chemotherapy resistance is the greatest contributor to mortality in advanced cancers and severe challenges remain in finding effective treatment modalities to cancer patients with metastasized and relapsed disease. High-grade serous ovarian cancer (HGSOC) is typically diagnosed at a stage where the disease is already widely spread to the abdomen and current standard of practice treatment consists of surgery followed by platinum-taxane based chemotherapy and maintenance therapy. While 90% of HGSOC patients show no clinically detectable signs of cancer after surgery and chemotherapy, only 43% of the patients are alive five years after diagnosis because of chemoresistant cancer.

This prospective, observational trial focuses on revealing major mechanisms causing chemoresistance in HGSOG patients and derive personalized treatment regimens for chemotherapy resistant HGSOC patients. The investigators recruit newly diagnosed advanced stage HGSOC patients who are then thoroughly followed during their cancer treatment. Longitudinal sampling includes digitalized H\&E stained histology slides mainly collected during routine diagnostics, fresh tumor \& ascites samples for next-generation sequencing/proteomics (WGS, RNA-seq, DNA-methylation, ATAC-seq, ChIP-seq, mass cytometry, etc.) and ex vivo experiments, plasma samples for circulating tumor DNA (ctDNA) analyses. Broad range of clinical parameters such as laboratory and radiologic parameters (e.g., FDG PET/CT), given cancer treatments and their outcomes are collected. Radiomic analyses are performed to PET/CT and CT scans. Long-term patient derived organoid lines are established from fresh tumor tissues. Actionable genomic alterations are searched.

The general objective is to establish a clinically useful precision oncology approach based on multi-level data collected in longitudinal setting, and translate the most potent and validated discoveries into clinical use. DECIDER project will produce AI-powered diagnostic tools, cutting-edge software platforms for clinical decision-making, novel data analysis \& integration methods, and high-throughput ex vivo drug screening approaches.

Read the detailed description

Specific aims include:

  • Develop tools and methods for personalized medicine approaches to cancer patients.
  • Develop open-source visualization and interpretation software that facilitate clinical decision making via data integration and interpretation of multilevel data from cancer patients.
  • Rapidly identify HGSOC patients who are likely to respond poorly to current therapies combining information on digitalized histopathology samples, genomic and clinical data with AI methods.
  • Deploy validated personalized medicine treatment options using longitudinal measurement and ex vivo organoid cultures from cancer patients in clinical care.
02

Conditions studied

  • High Grade Ovarian Serous Adenocarcinoma
  • High Grade Serous Carcinoma

Keywords

  • chemoresistance
  • personalized medicine
  • WGS
  • ctDNA
  • digital pathology
  • FDG PET/CT
  • bioinformatics
  • AI
  • ovarian cancer
  • tumor evolution
  • artificial intelligence
  • organoid
  • DNA methylation
  • radiomics
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

Inclusion criteria

  • Patients with a suspected ovarian cancer diagnosis treated at the Turku University Hospital
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion criteria

Exclusion Criteria:

  • Age \<18 years, too poor condition for active treatment (surgery, chemotherapy)
  • FDG PET/CT scan is not performed for patients with diabetes mellitus and poor glucose balance.
04

Study design

Phase
Not applicable
Primary purpose
Basic science
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
200 participants (estimated)

Study arms

  • Other
    HGSOC patients treated with Neoadjuvant chemotherapy (NACT)

    Diagnostic laparoscopy followed with 3-4 cycles of platinum-taxane NACT and interval debulking surgery (IDS). Treatment response is monitored with FDG PET/CT. IDS is followed by standard adjuvant therapy (ESGO/ESMO + local guidelines). Digital H\&E slides and WGS, RNAseq are obtained from performed surgeries including relapse operations/ascites drainages. Patients are followed with longitudinal ctDNA sampling.

    Genetic: WGS and RNA sequencing · Genetic: circulating tumor DNA (ctDNA) · Diagnostic Test: FDG PET/CT imaging

  • Other
    HGSOC patients treated with primary debulking surgery (PDS)

    PDS is followed by standard adjuvant therapy (ESGO/ESMO + local guidelines). Digital H\&E slides and WGS, RNAseq obtained from PDS and possible relapse operations/ascites drainages when performed. Patients are followed with longitudinal ctDNA sampling.

    Genetic: WGS and RNA sequencing · Genetic: circulating tumor DNA (ctDNA) · Diagnostic Test: FDG PET/CT imaging

Interventions

  • GeneticWGS and RNA sequencing
  • Geneticcirculating tumor DNA (ctDNA)
  • Diagnostic testFDG PET/CT imaging
05

What researchers measure

Primary outcomes

  1. Successful clinical translation

    The magnitude of successful clinical translation is measured by the number of times project-derived personalized medicine has impacted patients care by application of novel and existing biomarkers and therapies.

    Time frame: 5 years

  2. Successful prediction of patient outcome with AI methods

    Proportion of patients whose disease outcome (PFS, OS) is predicted correctly with digital histopathology images, genomic data and routine laboratory values

    Time frame: 5 years

Secondary outcomes

  1. Successful validation of potentially druggable genetic alterations

    Number of potentially druggable genetic alterations found and validated with in-vitro methods

    Time frame: 5 years

  2. Successful prediction of genomic features from tumor histology

    Number of genomic features that can be successfully recognized from tumor histology

    Time frame: 5 years

  3. Prediction of primary treatment response from tumor histology using H&E stained whole slide images and AI-based methods

    Number of patients whose outcome (primary therapy outcome, PFS) is predicted correctly

    Time frame: 5 years

  4. Establishment of an updated version of Chemoresponse score (CRS) for measuring histological effect in tumor tissue after chemotherapy

    Predictive power of the updated CRS at interval surgery is compared with traditional CRS

    Time frame: 5 years

06

Study locations

1 of 1 sites recruiting
  • Turku University Hospital
    Turku, 20520, Finland
    Recruiting
07

References and documents

08

Registry details

Key details

Study ID
NCT04846933
Lead sponsor
Turku University Hospital
Collaborators
University of Helsinki
Responsible party
Sponsor
First posted
Apr 15, 2021
Start date
Feb 1, 2012
Primary completion
Dec 2027 (estimated)
Completion
Dec 2029 (estimated)
Last update
Jan 16, 2025

Study contacts

Johanna Hynninen
Contact
johanna.hynninen@utu.fi
+358 50 5383554
Sampsa Hautaniemi
Contact
sampsa.hautaniemi@helsinki.fi
+358503364765
Sampsa Hautaniemi, DTech, Prof
study director · University of Helsinki
Johanna Hynninen, MD, PhD
principal investigator · Turku University Hospital

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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